Eyes on dementia: an overview of the interplay between eye movements and cognitive decline

The economic and disease burden of dementia is forecasted to continue increasing. Considering its cognitive effects, timely diagnosis is important in developing a stage-based treatment plan and gathering data to support advocacy efforts and plan healthcare and social services. Eye-tracking technology has emerged as an efficient diagnostic tool in clinical practice and experimental studies. This review aimed to comprehensively analyze various aspects of eye-tracking technology, including pupillometry parameters, eye movements, eye-tracking devices, and neuropsychological tools. We conducted a systematic review retrieving articles published in the last ten years from six databases. Our results provide a complex overview for each included form of dementia/cognitive decline in terms of patient characteristics (age, sex-disaggregated by included pathologies), inclusion and exclusion criteria, devices, and neuropsychological tools. We also summarized findings on fixation stability tasks, saccadic evaluation, pupillometry, scene perception, object recognition, spatial memory, eye-tracking video tasks, and visual search. The eye-tracking method has become more common in cognitive assessments.


INTRODUCTION
Cognitive decline, Alzheimer's disease, and other types of dementia pose significant challenges and represent a major public health issue, with recent estimates showing that 47 million individuals have dementia [1]. The global economic burden of dementia is estimated to reach US$818 billion by 2030 [2]. Dementia is a broad term that encompasses several types of cognitive disorders, including Alzheimer's disease (AD), vascular dementia (VaD), mixed Alzheimer's disease and vascular dementia (MAVD), Lewy body dementia (LBD), frontotemporal dementia (FTD), focal dementias, subcortical dementias, and secondary causes of dementia syndrome, such as intracranial lesions (ICLs) [3].
Alzheimer's disease is characterized by a gradual onset and incremental progression, with initial symptoms often characterized by short-term memory loss and unnoticed cognitive defi-ciencies. Conversely, vascular dementia is frequently linked to sudden vascular occurrences, and initial indications may include focal neurologic deficits. Lewy body disease (LBD) is characterized by a gradual onset and unpredictable advancement, accompanied by fluctuations in alertness and cognition. Focal atrophy in the frontal and/or anterior temporal lobes is a distinguishing characteristic of frontotemporal dementia alongside a gradual onset, with initial symptoms frequently manifesting as personality changes, reduced inhibitory control, speech impairment, and significant executive or language problems [4]. Considering the heterogeneity of dementia and its economic impact on society, timely diagnosis is of utter importance.
Eye-tracking technology has surfaced as a valuable and encouraging methodology for identifying and assessing cognitive dysfunction and monitoring its progression and severity [5]. Eye-tracking studies and the utilization of functional brain imaging techniques in the context of mental health and neurological JOURNAL of MEDICINE and LIFE disorder groups have substantially advanced our understanding of the impact of cognitive processes on saccadic eye movements [6]. The process of eye movement entails resolving the potential contradiction between top-down cognitive functions and bottom-up instinctive responses. This involves a conflict between the intentional exploration of our surroundings and the involuntary reaction to a visual or auditory stimulus that captures our attention. In an optimally functioning system, data travels from the visual cortex to the association cortex, followed by simultaneous and sequential projections to the premotor and motor cortex. There are also several back-and-forth connections between the cortex and the basal ganglia. The final collective output results from synaptic operations at multiple stages, generating a balance of information that either stimulates or suppresses neuronal activity. However, in cases of pathology, irregularities at varying stages could lead to distinctive patterns that have the potential to serve as a diagnostic indicator [7].
The main objective of this review article was to explore the application of eye-tracking technology in evaluating eye movements and pupillometry parameters across the spectrum of cognitive decline.

MATERIAL AND METHODS
This review aimed to investigate the role of eye-tracking technology in evaluating eye movements and pupillometry parameters in different stages of cognitive decline. To achieve this aim, several specific objectives were addressed: a. To provide an overview of the use of eye-tracking technology to evaluate eye movements and pupillometry parameters in different stages of cognitive decline, including its potential for early diagnosis and monitoring of cognitive decline. b. To examine the different types of eye movements, including saccades, smooth pursuit, antisaccades, and pupillometry, and their relationship with cognitive decline. c. To examine the role of eye-tracking technology in identifying early signs of cognitive decline and predicting dementia risk. d. To map neuropsychological instruments and eye-tracking devices.
We queried six databases (PubMed, Web of Science, Scopus, PsycINFO, Cochrane Library, and Embase). We included only articles written in English and published between 2013 and 2023. Limitation regarding geographical coverage was not applied. An additional inclusion criterion encompassed possible aims/objectives for the included studies: investigating the relationship between eye movements and pupillometry parameters, as evaluated by eye-tracking technology, and cognitive dysfunction in aging and dementia.
Studies published before 2013, non-English articles, non-primary research articles, and studies that did not focus on the use of eye-tracking technology to evaluate eye movements and pupil-lometry parameters in assessing cognitive decline were excluded. Additionally, articles that primarily addressed ophthalmological disorders were also excluded.
Based on the inclusion/exclusion checklist, two reviewers screened the abstracts (first stage) and read the full-text articles in order to establish the eligibility (second stage) for the final (third) stage of retrieving the elements of interest. Across all stages, disagreements were resolved with a third reviewer.
The information extracted from the included articles was recorded in a Microsoft Excel workbook and included the following: title, country, year, first author, age data (by study arms, as mean, or, if the mean was not reported, as range), sample size (for each study group), sex (predominant group, number or percentage), recruitment site, diagnosis (definition), patient inclusion and exclusion criteria, eye tracking device, eye movement outcome measures, test protocol applied, instruments/scales used and corresponding scores (for each group or overall, for each instrument).

RESULTS
Based on the search strategy, a total of 178 abstracts were retrieved. In the first stage, the abstracts were screened, resulting in 78 articles being included for full-text screening in the second stage. After the full-text screening, 35 articles were included in the review. Most studies were published in 2021 (n=7), while the least (n=2 for each year) were published in 2023, 2018, 2016, and 2013. The country with the highest number of studies was the United Kingdom (n=11).
As for the sample size, it ranged from 9 [8] to 108 for Alzheimer's disease [9], 7 and 20 patients for PCA [10,11], 12 [12,13] and 20 for bvFTD [14], and 15 [15] and 79 for mild cognitive impairment [16]. The highest and lowest mean age for patients with Alzheimer's disease was 77.8 [17] and 68.17 [18] years. For patients with posterior cortical atrophy (PCA), the mean ages ranged from 58.9 to 65.1 years [11,19], and for patients with behavioral variant frontotemporal dementia (bvFTD), the mean age ranged from 62.2 [14] to 68.83 years [18]. In the analyzed studies, female participants were predominant in 20 studies, while male participants were predominant in 8 studies (for the other studies, a breakdown by sex was not included). Most patients were recruited in memory clinics or hospitals. Additional details for each study screened can be found in Table 1. Among the studies included in the analysis, seven lacked clearly defined inclusion criteria, while ten lacked exclusion criteria. In some studies, inclusion and diagnosis definitions overlapped. Additional details for each study screened can be found in Table 2.
Our results indicate a high heterogeneity in the neuropsychological instruments used and the results obtained across the included articles. Thirty articles reported the type of neuropsychological instruments used, along with corresponding scores in some cases.
"rating of MCI in seven domains (memory, attention, language, visual-spatial, orientation, calculation, and executive function), AD -fewer than two lacunar ischemia (of diameter <1 cm); scores of <4 (Hachinski Ischemia Scale), no history of significant systemic or psychiatric conditions or traumatic brain injuries (compromising brain function)" "aMCI patients -impairment in a single non-memory domain (single, nonmemory domain MCI subtype) and impairment in two or more domains (multiple domains, slightly impaired MCI subtype)" "Amnesia mild-cognitive impairment: memory complaint (supported by proxy), objective memory impairment, normal general cognitive function, intact ADL, absence of dementia; Petersen Mini-Mental State Examination (MMSE) cutoff score" Lage et al.
"mild dementia stage (Global Deterioration Scale = 4); congruent neuropsychological and neuroimaging findings (brain CT and/or MRI), diagnoses confirmed by at least one type of biomarker, amyloid-PET, and/or CSF Alzheimer's disease core biomarkers; expert consensus (misclassification or heterogeneity)" "no cognitive complaints and showed normal results in all baseline evaluations, including normal levels of CSF; a biomarker result discordant with their clinical group, 1 patient with a clinical diagnosis of probable Alzheimer's disease dementia due to normal levels of CSF biomarkers and negative PiB-PET; and two bvFTD patients and two svPPA patients due to positivity in PiB-PET" "criteria for probable Alzheimer's disease, bvFTD, and svPPA; at least one type of Alzheimer's disease core biomarker" Craw-ford&Higham "probable Alzheimer's Disease (DSM IV), NINCDS criteria" -"probable Alzheimer's Disease (DSM IV), NINCDS criteria"     Table 3). The most frequently employed eye-tracking devices in the retrieved articles were different models of Tobii eye trackers (Pro spectrum system, TX300, ProX2-60, X120, TX300, 1750) and Eyelink (II, 1000, 1000 Plus). Prosaccade tasks were used in 9 studies, antisaccade tasks in 8 studies, visual search in 3 studies, fixation stability task and sinusoidal task, both in 2, while other applied protocols, such as Binding Task or Virtual Morris Water Navigation Task in one study (Table 4).
Tasks aimed at assessing fixation stability yield quantifiable measurements, such as the number of square wave jerks, small square wave jerk frequency, large square wave jerk frequency,

Author Inclusion criteria Exclusion criteria Diagnosis definition
Primativo et al. (2017) "consensus criteria for bvFTD, semantic dementia" "bvFTD -pattern of deficits being better accounted for by other non-degenerative nervous system or medical disorders, behavioral disturbance being better accounted for by a psychiatric diagnosis, biomarkers strongly indicative of Alzheimer's disease or other neurodegenerative process, SD -both impaired confrontation naming and single-word comprehension, at least 3 of the following other diagnostic features must be present (impaired object knowledge, surface dyslexia or dysgraphia, spared repetition, spared speech production), imaging (predominant anterior temporal lobe atrophy), hypoperfusion or hypometabolism" "bvFTD -a progressive deterioration of behavior and/or cognition by observation or history with three of the following symptoms being present (behavioral disinhibition, apathy, loss of sympathy or empathy, perseverative, stereotyped or compulsive/ritualistic behavior, hyperorality, and dietary changes, neuropsychological profile characterized by executive deficits with relative sparing of memory and visuospatial functions)"

Opwonya et al. (2022) -
"difficult to measure due to color blindness, poor vision, or sagging eyelids, or because they did not pass the preliminary exercise and calibration test" "MCI -Petersen criteria, CDR score of 0.5, neuropsychological test z scores were below -1.5 on at least one of five domain tests (according to age-, education-, and sex-specific norms)"

Hutchings et al. (2018) -
"possible bvFTD, atypical presentation, history of psychiatric or neurological conditions, substance abuse or medication (affecting the central nervous system)" "consensus following a clinical assessment with a behavioral neurologist, comprehensive neuropsychological assessment, structural brain imaging and met current consensus criteria for bvFTD" Russell et al. Fernandez & Parra (2021) "at least one caregiver providing regular care and support, diagnosis of ophthalmologic diseases such as glaucoma, visually significant cataract, or macular degeneration" "psychiatric diseases, traumatic brain injury, cardiovascular disease, brain tumors, or infectious diseases of the CNS; suffered from any medical conditions other than dementia that could account for, or interfere with, their cognitive functioning; evidence of vascular lesions in CT or MRI scans, evidence for an Axis I diagnosis (e.g., major depression or drug abuse) as defined by the DSM-IV" "mild Alzheimer's Clinical Syndrome -(DSM-IV); subjects' visual acuity was 20/20 or corrected to 20/20 as confirmed by an ophthalmological assessment" El Haj et al.
"amnestic form of AD dementia -experienced neurologist or geriatrician (criteria of the National Institute on Aging-Alzheimer's Association)" "significant psychiatric or neurological illnesses, alcohol or drug use, or a history of clinical depression, major visual or auditory acuity difficulties, administered drugs (e.g., tropicamide) -alter pupillary dilatation" "amnestic form of AD dementiaexperienced neurologist or geriatrician (criteria of the National Institute on Aging-Alzheimer's Association)"   "EEG -data quality issues; eAD group had evidence of non-degenerative dementia (e.g., inflammatory, metabolic, or vascular dementia), nonamnestic MCI or cognitive impairment of doubtful origin, or severe medical conditions that limited their ability to participate in the study" "blinding process for patients' performance -neurologist"  [10,20,21]. The findings from fixation stability paradigms reveal distinct patterns of impairment across different forms of dementia. Decreased periods of fixation have been observed in both the PCA and typical Alzheimer's disease groups when compared to the control. Intriguingly, in PCA, this decrease in the fixation period was accompanied by an elevated frequency of large intrusive saccades, whereas typical Alzheimer's disease was linked to an increased frequency of square wave jerks [10]. Behavioral variant frontotemporal dementia was associated with impaired fixation stability compared to control participants [21]. Furthermore, individuals with young-onset Alzheimer's disease (YOAD) exhibited an increased frequency of large intrusive saccades in conjunction with reduced fixation duration while performing the fixation stability task. Patients with YOAD displayed a significant negative correlation between their performance in object decision, fragmented letters, and dot-counting tests and the presence of large intrusive saccades [20].
One study revealed that 80% of patients with posterior cortical atrophy (PCA) exhibited oculomotor impairment in prosaccade tasks, which was in stark contrast to the 17% of patients with typical Alzheimer's disease and the 5% of control participants [10]. Notably, a considerable distinction was found between the groups of individuals with PCA and those with typical Alzheimer's disease regarding saccade amplitude error, with a sensitivity of 93.8% and specificity of 83.3% [10]. Interestingly, in amnestic mild cognitive impairment (aMCI) patients, the gap and overlap prosaccade paradigm showed impaired saccadic gains, making it a sensitive measure for distinguishing between aMCI and healthy controls [22]. There was no significant difference in pro-saccade task performance between patients with bvFTD and controls except for the vertical overlap saccadic task [21]. For individuals with young-onset Alzheimer's disease, impaired performance was observed in the pro-saccade task, characterized by reduced accuracy, longer fixation times, and greater saccadic movements required to fixate the target. Furthermore, these metrics negatively correlated with performance on several neuropsychological tests [20]. Lastly, patients with mild cognitive impairment (MCI) were found to have significantly longer latencies in prosaccade tasks compared to healthy controls [23].
The antisaccade task demonstrated alterations in the process of healthy aging and the initial phases of neurodegeneration. Key hubs in the oculomotor network, particularly the right lateral nodes linked to the right lateral frontal eye field (rlatFEF), have been identified as critical for efficient executive functioning during aging. Dysfunction in these hubs and network connections may be a potential biomarker for cognitive decline [24]. The process of aging is associated with alterations in both inhibitory control (IC) and working memory (WM), as further demonstrated by an increased antisaccade error rate [25]. This behavior is also observed in individuals diagnosed with amnestic mild cognitive impairment. These patients exhibit more errors and omissions and make fewer corrections in their saccade behavior compared to controls [26].          Table 3.

Continued IV. Neuropsychological instruments used and corresponding scores by study groups
with MCI showed a trend toward increased correction latencies [16]. The antisaccade task presented the potential to differentiate between aMCI and non-amnestic MCI (naMCI) [27]. Distinct oculomotor patterns have been observed in patients with Alzheimer's disease, behavioral variant frontotemporal dementia, and semantic variant primary progressive aphasia (svPPA). BvFTD patients, in particular, exhibit significant deficits in the antisaccade and memory saccade tasks, which heavily rely on frontal lobe functioning and require cognitive demand [18]. These oculomotor patterns involve the dorsolateral prefrontal and parietal cortices, as well as the striatum [28]. In a longitudinal assessment with eye tracking, patients with AD initially had slower reaction times than the control group. However, after 12 months, both groups displayed similar reductions in reaction times to the gap stimulus compared to the overlap stimulus. Moreover, there was a general improvement for both groups in the accuracy of saccades and reaction time speed after 12 months [29].
Individuals diagnosed with AD or mild cognitive impairment had a higher number of oblique microsaccades than individuals without these conditions [30].
Pupillometry studies have shown significant potential in assessing cognitive disorders. For example, in a binding task, healthy controls exhibited significant pupil dilation during the Bound Colours condition compared to the Unbound Colours condition. However, this differentiation was not observed in individuals with Alzheimer's clinical syndrome. These aberrant pupil responses effectively differentiated Alzheimer's clinical syndrome patients from healthy controls with 100% sensitivity and specificity [31]. Interestingly, in another study focused on assessing pupil size during complex cognitive tasks such as forward spans, backward spans, and counting, patients with AD showed fewer variations in pupil size across the conditions compared to the control participants [32].
Regarding scene perception abilities, the eye-tracking evaluation showed that patients with posterior cortical atrophy struggle to focus on task-relevant regions, highlighting the interplay between cognition and perception [33]. People recall object locations better than their identities using the change detection eye tracking model, implying stronger visual working memory for real-world scenes than object recognition. Interestingly, this capacity to process and remember visual-spatial information in naturalistic settings persists in individuals with mild cognitive impairment, indicating that their condition does not hinder this aspect of cognition [34]. In a visual memory task, presymptomatic carriers of familial Alzheimer's disease (FAD) showed increased reliance on fixation time for target localization. Whereas only symptomatic individuals showed memory function deficits, indicating potential spatial memory issues in presymptomatic FAD carriers [35].
Eye-tracking scores, calculated from fixation duration during a video observation task, significantly decreased in MCI and AD, correlating strongly with MMSE scores. The test effectively differentiated between NC, MCI, and AD, particularly in memory and reasoning tasks [36]. Similarly, another eye-tracking video task showed that patients with AD exhibited an increased number of fixations and longer fixation duration in perceptual and working spaces than normal control (NC) participants. This was especially evident in patients with early-onset AD (EOAD), who had more fixations and higher switching than both late-onset AD (LOAD) patients and NC participants [37]. Video-based eye-tracking tasks also showed excellent diagnostic accuracy in distinguishing MCI subjects from healthy controls, comparable to the MMSE scores [38].
In a visual search eye-tracking task based on fixation parameters, patient groups displayed higher interest area fixation count than controls, with a pronounced disparity between AD participants and the aMCI or subjective cognitive decline (SCD) group [39]. Similarly, patients with MCI and AD showed increased screen fixations and longer fixation durations during target searches compared to controls, often focusing more on distractors. Machine learning techniques were able to effectively differentiate between control participants and those with AD [40]. In parameters related to spatial accuracy, as saccade error (the deviation of the final position of the gaze from the target, measured as positive or negative error) and pursuit error (the difference between the target position and the gaze position during a pursuit test); parameters related to time, as latency (defined by the time delay between the appearance of a peripheral target and the onset of the ocular movement) and pursuit gain (the rate between ocular velocity and target velocity during a pursuit test); parameters related to success, as the percentage of correct memory saccades in the memory saccade test and, in the antisaccade test, the percentage of correct antisaccades, corrected erroneous antisaccades (corrected antisaccades) and successful antisaccades, which represent the sum of correct and corrected antisaccades prosaccade task, sinusoidal smooth pursuit task, antisaccade task, memory saccade task Gazefinder NP-100 (JVC KENWOOD Corporation, Kanagawa, Japan) % fixation duration within the ROI task movies and pictures  the case of bvFTD, visual search patterns were characterized by reduced accuracy, longer response times, and an elevated occurrence of eye movements, both in terms of quantity and duration [41].
Other complex eye-tracking tasks have proven effective in studying the visual behavior of cognitively impaired patients. One such method involves reading studies using eye-tracking techniques. For example, an eye-tracking adapted version of the King-Devick reading test observed notable distinctions in sac-cadic duration and amplitude between control individuals and those with MCI or AD dementia [42]. In addition to reading tasks, eye-tracking has been employed in visual-spatial decision-making tasks. In one study, patients with AD displayed higher error rates than individuals with aMCI and the control group [43]. The utility of eye-tracking extends even further to complex tasks such as visual attention paradigms. For instance, in a study examining visual attention scanning in Alzheimer's disease, patients who spent less time viewing new images presented a high-JOURNAL of MEDICINE and LIFE er reduction in neuropsychological evaluation scores [44]. This suggests that the inclination towards novelty, evaluated through eye-tracking technology, could be a potential marker for disease progression and cognitive decline [44]. Furthermore, individuals with aMCI exhibited difficulties in spatial learning, as demonstrated in an eye-tracking adapted Morris Water navigation task [8]. Interestingly, eye-tracking data obtained from a 3D Visual Paired Comparisons (VPC) task revealed distinct differences in eye-tracking traits between people with Alzheimer's Disease (PwAD) and healthy controls (HCs), as evident from the fixation heatmaps [45].

DISCUSSION
Our review provides a comprehensive overview of eye-tracking technologies, eye movements, and neuropsychological instruments used in patients with different stages of cognitive decline. Most studies included cohorts of patients who have Alzheimer's Disease. A recent systematic analysis investigating the global burden of AD and other types of dementia revealed significant increases in incidence and prevalence rates between 1990 and 2019. The analysis reported a significant increase of 147.95% in incidence and 160.84% in prevalence. Furthermore, the number of deaths attributed to dementia increased by 1.06 million during this period [46]. Most cases of AD and dementia were reported among women, and the burden of these conditions was higher in high-income countries [46].
The Mini-Mental State Examination (MMSE) was the most commonly used scale in the retrieved studies [10,33]. The MMSE is a cognitive screening tool consisting of 11 questions that assess various cognitive domains such as orientation, attention/concentration, memory, language skills, and visuospatial abilities [47]. It has been extensively validated in multiple languages and has been utilized in patients diagnosed with various pathologies, including Parkinson's disease, Alzheimer's disease, traumatic brain injury, and depression, as well as in different clinical settings such as clinical practice, clinical trials, and epidemiological studies [48][49][50]. However, some challenges related to acceptability, ease of scoring, and the influence of factors like age, education, language, and culture have been identified [51].
The second most used instrument, the Clinical Dementia Rating (CDR), is utilized for assessing the stages of dementia. It evaluates various domains of interest, including memory, orientation, judgment and problem-solving, community affairs, home and hobbies, and personal care. The CDR assigns five ratings, ranging from "Healthy CDR 0" to "Severe Dementia CDR 3.0", to indicate the severity of dementia. Although this instrument has demonstrated good inter-reliability, it has a difficult scoring system [52]. Nevertheless, the CDR has been validated in culturally diverse populations and is widely employed in clinical practice and clinical trials [53][54][55][56].
The Trail Making Test (TMT) was the third most commonly used assessment tool, followed by Digit Span and the Geriatric Depression Scale (GDS). The TMT is a neuropsychological test that evaluates memory and executive functioning by measuring the time taken to connect consecutive circles on a page (TMT-A) and to switch between numbers and letters (TMT-B). Average and deficient scores for TMT-A range from 29 to 78 seconds, and for TMT-B, 75 to 273 seconds [57]. This test, from which other versions have been derived, is available in both electronic and paper-based versions and has been validated in multiple countries and different age segments [58][59][60][61][62]. Digit Span, constructed on the work of Gottfried Leibniz on cognition, is one the most used subtests to assess short and working memory by repeating a row of digits forward and backward [63,64]. It is incorporated in the WAIS-IV (Wechsler Adult Intelligence Scales) and has been validated by taking into account different indicators, such as "age-corrected scaled scores" or "various time-to-recite measures" [65,66]. GDS is a 30-item binary self-reported measure assessing the affective and cognitive domains for signs of depression (higher scores corresponding to severe cases of depression) [67]. It has been extensively used in various populations, including hospitalized and non-hospitalized elderly individuals with cancer, traumatic brain injury, and stroke. The scale has been translated and validated in multiple languages, and a shorter 15-item version (GDS-S) has been derived to reduce respondent fatigue [68].
Diverse eye-tracking protocols have been employed to evaluate various oculomotor functions and visual processing abilities in individuals experiencing cognitive dysfunction. The review provides an overview of various tasks that are frequently utilized in research studies. These tasks encompass the 3D VPC task, spatial decision task, fixation stability assessment, saccade assessment under gap and overlap conditions, sinusoidal pursuit tasks, antisaccade tasks, memory-guided saccade tasks, and object-localization VSTM tasks [10, 20-22, 24, 30, 33, 35, 45, 69, 71, 73, 78, 80-84]. Furthermore, the integration of eye-tracking technology with video stimuli has facilitated the investigation of various cognitive processes, including emotion recognition, passive viewing of faces and scene stimuli, visual search, visual attention, visual processing, and reading tasks such as virtual Morris Water Navigation [36,37,39,41,44,75,75,76]. This review highlights the wide range of eye-tracking protocols available, which offer researchers a thorough understanding of how to investigate cognitive dysfunction related to dementia. Through the utilization of these protocols, researchers can augment their comprehension of the pathophysiology of dementia and potentially make valuable contributions to advancing more efficacious diagnostic and therapeutic methodologies.
Fixation stability tasks include the evaluation of gaze fixation stability, wherein various parameters such as square wave jerks, fixation duration, and saccade frequencies are measured. Research has indicated that various manifestations of dementia correlate with compromised fixation stability [10,20]. Both PCA and typical Alzheimer's disease are characterized by a reduction in fixation duration. However, PCA is characterized by a higher occurrence of large saccades, whereas AD is associated with an increased prevalence of square wave jerks [10]. Impaired fixation stability has been observed in individuals diagnosed with bvFTD [41]. Individuals diagnosed with YOAD exhibit a heightened occurrence of large saccades and a decrease in the duration of fixation, both of which are inversely associated with cognitive test performance [20]. Research studies have demonstrated that individuals diagnosed with PCA exhibit deficits in their ability to perform saccadic evaluation tasks, indicating impairments in their oculomotor function [10]. Similarly, patients diagnosed with amnestic mild cognitive impairment display compromised saccadic gains, further highlighting the impact of cognitive impairment on oculomotor abilities [22]. Antisaccade tasks have been employed as a means of distinguishing between cognitive disorders, specifically amnestic mild cognitive impairment (aMCI) and non-amnestic mild cognitive impairment (naMCI) [22]. Research on pupillometry has demonstrated promise in distinguishing individuals with AD from those without the condition. [32]. Eye-tracking has been employed to evaluate various cognitive tasks in individuals with dementia, including scene perception, object recognition, spatial memory, video tasks, and visual search [34,72,81,85]. This method has unveiled unique eye movement patterns and holds promise as a diagnostic tool.

CONCLUSION
Our review mapped the role of eye-tracking technology in evaluating eye movements and pupillometry parameters, combined with several scales, across different stages of cognitive decline associated with various forms of dementia. Although we included the most recent articles, a constant update is needed to account for increasing trends of dementia, healthcare digitization, and combinations of eye-tracking methodologies.